End-joining in yeast

The DNA-repair mechanism referred to as non-homologous end-joining (NHEJ) involves the Ku proteins (Ku70 and Ku80), DNA ligase IV and Lif1/XRCC4. Meiotic cells down-regulate NHEJ, to favour homologous recombination. In the December 6 Nature, Maria Valencia and colleagues describe a mechanism for the down-regulation of NHEJ in meiosis-competent MATa/MATα diploid Saccharomyces cerevisiae cells (Nature 2001, 414:666-669). They found that LIF1 (encoding ligase-interfacing factor 1) expression was decreased in the diploid strain, but LIF1 overexpression only partially restored NHEJ. Microarray analysis of mating-type mutant strains led them to identify a novel gene, NEJ1 (non-homologous end-joining defective). Deletion of NEJ1 reduces NHEJ, and the gene is strongly mating-type-regulated. The promoter regions of both the LIF1 and NEJ1 genes contain binding sites for the Mata1-Matα2 repressor. Valencia et al.suggest that NEJ1 affects the cellular localization of LIF1 during meoisis. It will be interesting to see whether similar regulation of NHEJ components occurs during meiosis in mammalian cells.